Suicide is one of the major preventable causes of death in the United States. Over 25,000 individuals commit suicide annually and ten times that number make suicide attempts. Considerable efforts have been directed toward preventing suicide and identifying those individuals who are at risk. Most studies aimed at identifying suicide risks have focused on personality, diagnostic, demographic or social factors. While these variables may show a relationship with suicide, these relationships are typically weak and consequently of limited clinical utility. Recent biochemical investigations of suicide behavior have shown that suicide victims and suicide attempters have alterations in serotonergic function. These findings may hold promise for increased prediction of suicide and ultimately, prevention of the act. However, the studies reporting these alterations have been narrow in focus, have used small samples, and have investigated only single aspects of biochemical dysfunction. The purpose of this project is to conduct a large study of biochemical aspects of suicide behavior. Specifically, we are proposing to systematically investigate the role of serotonergic function in suicide attempts. The major questions to be addressed are: 1) Do psychiatric patients who have attempted suicide differ from patients who have not attempted suicide on direct measures of serotonergic function (e.g., CSF levels of 5-HIAA) and by indirect measures (e.g., dexamethasone suppression of cortisol)? 2) Is there an interaction of serotonergic function, diagnosis and suicide behavior? 3) Does the recency of a suicide attempt have an effect on serotonergic function? 4) Can a profile consisting of biochemical and behavioral factors be developed which may more accurately identify individuals at risk? This project will be conducted by measuring serotonergic function in a large sample of psychiatric patients who have attempted suicide and compare it with a diagnostically matched group who have never made a suicide attempt. This research will help answer in a definitive manner the degree to which dysfunction of the serotonergic system is implicated in suicide behavior. These findings may ultimately be useful in improving the prediction of suicide and lead to the development of a pharmacologic treatment.